Lukasiewicz P D, Shields C R
Department of Ophthalmology and Visual Sciences and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurophysiol. 1998 Jun;79(6):3157-67. doi: 10.1152/jn.1998.79.6.3157.
This study addresses how gamma-aminobutyric acid-A(GABAA) and GABAC receptors confer distinct temporal properties to neuronal synaptic responses. The retina is a model system for the study of postsynaptic contributions to synaptic responses because GABAergic amacrine cells synapse onto neurons, which have different combinations of GABAA and GABAC receptors. It is not known, however, how GABAA versus GABAC receptors influence the time course of retinal synaptic responses or what proportion of inhibitory input is mediated by each receptor type. We examined the time courses of synaptic responses mediated by GABA receptors in ganglion and bipolar cells by recording currents evoked by activating amacrine cells with a stimulating electrode in the salamander retinal slice. The pharmacologically isolated, GABAergic synaptic currents were long-lasting in bipolar cells and relatively brief in ganglion cells. The receptors that mediated these temporally distinct synaptic responses exhibited different pharmacological properties. In ganglion cells, GABAergic synaptic currents were abolished by the GABAA receptor antagonists bicuculline or SR95531. In bipolar cells, the GABAC receptor antagonist 3-aminopropyl[methyl]phosphonic acid (3-APMPA) largely blocked GABAergic synaptic responses; the remaining response was blocked by bicuculline or SR95531. The GABAA receptor component of the bipolar cell response was relatively brief compared with the GABAC receptor component. Puffing GABA onto ganglion cell dendrites or bipolar cell terminals yielded similar pharmacological and kinetic results, indicating that transmitter release differences did not determine the response time courses. Moreover, the GABAC receptors on bipolar cells may be different from those reported in rat or fish retina because imidazole-4-acetic acid (I4AA), which acts as an antagonist in these preparations, acts as an agonist in salamander. Our data show that the prolonged synaptic responses in bipolar cells were mediated predominantly by GABAC receptors, whereas transient synaptic responses in ganglion cells were mediated by GABAA receptors.
本研究探讨γ-氨基丁酸A（GABAA）受体和GABAC受体如何赋予神经元突触反应不同的时间特性。视网膜是研究突触后对突触反应贡献的模型系统，因为γ-氨基丁酸能无长突细胞与具有不同GABAA和GABAC受体组合的神经元形成突触。然而，尚不清楚GABAA受体与GABAC受体如何影响视网膜突触反应的时间进程，以及每种受体类型介导的抑制性输入占比是多少。我们通过在蝾螈视网膜切片中用刺激电极激活无长突细胞来记录电流，研究了神经节细胞和双极细胞中由GABA受体介导的突触反应的时间进程。药理学分离的γ-氨基丁酸能突触电流在双极细胞中持续时间长，在神经节细胞中相对短暂。介导这些时间上不同的突触反应的受体表现出不同的药理学特性。在神经节细胞中，GABAA受体拮抗剂荷包牡丹碱或SR95531可消除γ-氨基丁酸能突触电流。在双极细胞中，GABAC受体拮抗剂3-氨基丙基[甲基]膦酸（3-APMPA）可大部分阻断γ-氨基丁酸能突触反应；其余反应可被荷包牡丹碱或SR95531阻断。与GABAC受体成分相比，双极细胞反应的GABAA受体成分相对短暂。将GABA吹入神经节细胞树突或双极细胞终末产生了相似的药理学和动力学结果，表明递质释放差异并未决定反应时间进程。此外，双极细胞上的GABAC受体可能与大鼠或鱼类视网膜中报道的不同，因为在这些制剂中起拮抗剂作用的咪唑-4-乙酸（I4AA）在蝾螈中起激动剂作用。我们的数据表明，双极细胞中延长的突触反应主要由GABAC受体介导，而神经节细胞中的瞬时突触反应由GABAA受体介导。
